Statins Underused in Veterans with Severely Elevated Cholesterol

MedicalResearch.com Interview with:

Fatima Rodriguez, MD, MPH Division of Cardiovascular Medicine Stanford University Stanford, CA 94305-5406,

Dr. Rodriguez

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. Continue reading

Statins: Large Disparity Between US/Canadian/UK and European Guidelines

MedicalResearch.com Interview with:

Borge G. Nordestgaard,

Borge G. Nordestgaard

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.

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Frequent Take-Out Food Linked To Increased Cholesterol and Obesity in Children

MedicalResearch.com Interview with:

Dr. Angela S Donin Population Health Research Institute, St George’s University of London, London, UK

Dr. Donin

Dr. Angela S Donin
Population Health Research InstituteSt 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.

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Praluent May Reduce Need For Apheresis In Some Patients With Familial Hypercholesterolemia

MedicalResearch.com Interview with:

Dr. Jay Edelberg VP Head of CV Development and Head Global CV Medical Affairs

Dr. Edelberg

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.

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Cellular Protein Nrf1 Protects Against Fatty Liver

MedicalResearch.com Interview with:

Gokhan S. Hotamisligil MD PhD

Dr. Hotamisligil

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. Continue reading

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 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”.

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Familial Hypercholesterolemia Diagnosed Through EHR and Genetics Data

MedicalResearch.com Interview with:

Michael F. Murray MD Geisinger Health System Danville, PA 17822

Dr. Michael Murray

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.

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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.

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Cholesterol: What’s Bad For Your Heart Is Bad For Your Tendons

Jamie Gaida, PhD Assistant Professor Discipline of Physiotherapy University of Canberra

Dr. Jamie Gaida

MedicalResearch.com Interview with:
Jamie Gaida, PhD
Assistant Professor
Discipline of Physiotherapy
University of Canberra

Medical Research: What is the background for this study? What are the main findings?

Dr. Gaida: Cholesterol is essential for life but having too much circulating in your blood increases cardiovascular disease risk. A growing collection of evidence indicates that metabolic health (i.e. cholesterol and diabetes) is linked to musculoskeletal injuries.

Tendons connect muscle to bone, and tendinopathy is condition where a person feels pain when using their tendons. People with Achilles tendinopathy experience pain when walking or when running, which limits their ability to be physically active. Tendinopathy also affects other tendons throughout the body, such as the rotator cuff tendons of the shoulder.

This research identified all published research on the link between cholesterol levels and tendinopathy. We used a statistical technique called meta-analysis to combine these studies, which showed that cholesterol levels are linked to tendinopathy. However, the most interesting finding was that the pattern of cholesterol changes seen with tendinopathy matched the pattern of cholesterol changes that increase cardiovascular disease risk. It seems that what is bad for you heart is bad for your tendons.

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“Bad Cholesterol” LDL-C Linked to Aortic Valve Disease

George Thanassoulis, MD MSc FRCP(C) Director, Preventive and Genomic Cardiology FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien Assistant Professor of Medicine, McGill University McGill University Health Center Montreal, QCMedicalResearch.com Interview with:
George Thanassoulis, MD MSc FRCP(C)

Director, Preventive and Genomic Cardiology
FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien
Assistant Professor of Medicine, McGill University
McGill University Health Center Montreal, QC

Medical Research: What is the background for this study? What are the main findings?

Dr. Thanassoulis: Although LDL-C (i.e. bad cholesterol) has been linked with aortic valve disease in several prior reports, randomized trials to lower cholesterol in aortic valve disease were not effective suggesting that cholesterol may not be important in valve disease.

To address this, we performed a Mendelian randomization study, that showed that a genetic predisposition to LDL-C, was associated with both calcium deposits on the aortic valve and aortic stenosis (I.e. Valve narrowing).  These results can be viewed as the effect of a life-long increase in LDL-C on the incidence of aortic valve disease and suggest that increases in LDL-C cause aortic stenosis.   Continue reading

Evolocumab Markedly Reduced LDL in Hypercholesterolemia

Professor F. J. Raal FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD Director, Carbohydrate & Lipid Metabolism Research Unit Professor & Head, Division of Endocrinology & Metabolism Faculty of Health Sciences, University of the Witwatersrand Johannesburg Hospital Johannesburg South AfricaMedicalResearch.com Interview with:
Professor F. J. Raal
FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD
Director, Carbohydrate & Lipid Metabolism Research Unit
Professor & Head, Division of Endocrinology & Metabolism
Faculty of Health Sciences, University of the Witwatersrand
Johannesburg Hospital Johannesburg South Africa

Medical Research: What are the main findings of the study?

Dr. Raal: Heterozygous familial hypercholesterolaemia (HeFH)  is one of the most common inherited disorder in man affects between 1:250 to 1:300 persons worldwide. Thus, there are likely more than 3 million patients with heterozygous familial hypercholesterolaemia in the United States and Europe alone. The RUTHERFORD-2 study was a large world-wide multinational study  of the use of the PCSK9-inhibitor, evolocumab, in over 300 patients with heterozygous familial hypercholesterolaemia (HeFH). Evolocumab administered either 140 mg biweekly or 420 mg monthly as a subcutaneous injection, much like an insulin injection, was well tolerated with minimal side effects,  and markedly reduced levels of LDL cholesterol or “bad cholesterol”  by over 60% compared to placebo.

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Fenofibrate Improves Cholesterol Profile in Diabetes

MedicalResearch.com Interview with:
Prof. Michael d’Emden
Endocrine Research Unit
Royal Brisbane Hospital, Brisbane, Australia

Medical Research: What are the main findings of the study?

Prof. d’Emden: Our study is the largest trial of women having type 2 diabetes assessing the role of a fibric acid derivative, in this case fenofibrate, ever conducted.  There were 3657 female subjects randomized to placebo or fenofibrate.  The study demonstrated greater reductions in women of total cholesterol, triglycerides and LDL-cholesterol and greater increases in HDL-cholesterol.  In women, fenofibrate decreased total cardiovascular end-points by 30% compared with only 13% in men, although there was no-treatment-by-sex interaction.  The majority of end points assessed revealed a consistent trend to increased benefit being seen in women.

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Niacin Pill Did Not Reduce Heart Attacks or Strokes, but Did Increase Side Effects

Professor Jane Armitage Professor of Clinical Trials and Epidemiology Clinical Trial Service Unit, Oxford Cardiovascular Science Oxford, United KingdomMedicalResearch.com Interview with:
Professor Jane Armitage
Professor of Clinical Trials and Epidemiology
Clinical Trial Service Unit, Oxford Cardiovascular Science
Oxford, United Kingdom


Medical Research: What are the main findings of the study?

Prof. Armitage: The study showed that adding extended release niacin with laropiprant (to reduce the flushing) to standard treatment including statins in people with heart disease or strokes did not improve their outcome or reduce the risk of recurrent heart attacks or strokes.
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Evolocumab for LDL Cholesterol Reduction in Statin-Treated Patients

Medidr_jennifer_robinsoncalResearch.com Interview with:
Jennifer G. Robinson, MD, MPH
Professor ,Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
College of Public Health
University of Iowa
Iowa City, IA 52242-2007

MedicalResearch: What are the main findings of the study?

Dr. Robinson: The PCSK9 antibody, evolocumab, reduced LDL (or bad) cholesterol by about 65-70% regardless of the dose or type of statin used. This is a greater percentage reduction than ezetimibe, another drug used to lower LDL cholesterol in statin-treated patients, which lowered LDL cholesterol 15-20%. Side effects of evolocumab were similar to those for ezetimibe or placebo.

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New Statins Guidelines Will Prevent More Heart Attacks, Stroke But Treat More Who May Not Need Them

Michael J. Pencina, PhD Professor of Biostatistics and Bioinformatics Director of Biostatistics Duke Clinical Research Institute Durham, NC 27710 MedicalResearch.com Interview with:
Michael J. Pencina, PhD
Professor of Biostatistics and Bioinformatics
Director of Biostatistics
Duke Clinical Research Institute
Durham, NC 27710

MedicalResearch.com: What motivated your research?

Dr. Pencina: After the new guidelines were issued last November, we were intrigued by the change in treatment philosophy from that based on cholesterol levels (used by the “old guidelines” known as NCEP ATPIII) to one based on 10-year risk of cardiovascular disease (used by the new AHA-ACC guidelines).  We were curious what the practical consequences of this shift would be.

Furthermore, the media quoted a lot of experts making educated guesses on the impact.  We realized that this question can be answered much more precisely based on the NHANES data.

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Gene Variant Influencing Cholesterol and Myocardial Risk Discovered

dr_cristen_j_willerMedicalResearch.com Interview with:
Cristen J. Willer, PhD
Assistant Professor
Division of Cardiovascular Medicine, Dept of Internal Medicine
Dept of Human GeneticsDept of Computational Medicine and Bioinformatics
University of Michigan Ann Arbor, MI 48109-5618

MedicalResearch.com: What are the main findings of the study?

Dr. Willer: We wanted to find new genes related to heart disease, so we examined the DNA of approximately 10,000 Norwegian individuals and found 10 genes that are important regulators of blood cholesterol levels. Nine of these were well known to be related to lipids, but one gene was new.  It turned out to be in a region we’d previously noticed to be related to cholesterol, but it was a big region and we hadn’t been able to pinpoint the gene yet.  Using this new approach, focusing on DNA differences that result in slightly different proteins in people, we zeroed in on the gene.  We then altered this gene in mice, and saw the predicted changes in cholesterol levels in mice.
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High LDL, Low HDL Levels and Elevated Brain Amyloid

MedicalResearch.com Interview with:
Dr. Bruce Reed PhD Professor of Neurology, Associate Director UC Davis Alzheimer's Disease Center Davis, CA 95616
Dr. Bruce Reed PhD

Professor of Neurology,
Associate Director UC Davis Alzheimer’s Disease Center
Davis, CA 95616

MedicalResearch.com: What are the main findings of the study?

Dr. Reed: We found that high LDL cholesterol and low HDL cholesterol in blood  were both associated with higher amyloid deposition in the brain.  This is potentially very important because the deposition of amyloid seems to be a critical step that kicks off a whole chain of events that eventually lead to Alzheimer’s disease.  It is widely believed (although not proven) that if this deposition of amyloid could be blocked that we could greatly decrease the incidence of Alzheimer’s.  The connection to cholesterol is exciting because we know a fair amount about how to change cholesterol levels.  A great deal more research needs to be done, but this does suggest a potential new path toward trying to prevent AD.

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