Older Patients May Benefit from Combination of Simvastatin-Ezetimibe After Acute Coronary Syndrome

MedicalResearch.com Interview with:

Richard G. Bach, MD FACC Professor of Medicine Washington University School of Medicine Director, Cardiac Intensive Care Unit Director, Hypertrophic Cardiomyopathy Center Barnes-Jewish Hospital St. Louis, MO 63110

Dr. Bach

Richard G. Bach, MD FACC
Professor of Medicine
Washington University School of Medicine
Director, Cardiac Intensive Care Unit
Director, Hypertrophic Cardiomyopathy Center
Barnes-Jewish Hospital
St. Louis, MO 63110

MedicalResearch.com: What is the background for this study?

Response: Elderly patients represent the largest group of those hospitalized for an acute coronary syndrome, and age is an important marker of increased risk. The risk of death and recurrent cardiovascular events is greatest among the elderly. High intensity lipid lowering by statins has been shown to reduce the incidence of recurrent cardiovascular events after an acute coronary syndrome in general, but there remains limited data on efficacy and safety of that treatment in the elderly, and guidelines do not routinely advocate higher intensity treatment for patients older than 75 years. In practice, older age has been associated with a lower likelihood of being prescribed intensive lipid lowering therapy. IMPROVE-IT evaluated the effect of higher-intensity lipid lowering with ezetimibe combined with simvastatin compared with simvastatin-placebo among patients after ACS, and observed that ezetimibe added to statin therapy incrementally lowered LDL-cholesterol level and improved CV outcomes. IMPROVE-IT enrolled patients with no upper age limit, which gave us the opportunity to examine the effect of age on outcome on the benefit of more intensive lipid lowering with ezetimibe combined with simvastatin vs. simvastatin monotherapy.

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Lipid Control Treatment Gap in Patients with Atherosclerotic Disease

MedicalResearch.com Interview with:

Guanmin Chen MD PhD MPH Senior Biostatistician Research Facilitation, Alberta Health Services Adjunct Research Assistant Professor University of Calgary

Dr. Chen

Guanmin Chen MD PhD MPH
Senior Biostatistician Research Facilitation, Alberta Health Services
Adjunct Research Assistant Professor
University of Calgary 

Co-authors: Guanmin Chen, PhD, MD, MPH, Megan S. Farris, MSc, Tara Cowling, MA, MSc, Stephen M. Colgan, PhD, Pin Xiang, PharmD, Louisa Pericleous, PhD, Raina M. Rogoza, MSc, Ming-Hui Tai, MSc, PhD, and Todd Anderson, MD 

MedicalResearch.com: What are the main findings?

Response:

  • Atherosclerotic cardiovascular disease (ASCVD) remains a significant cause of morbidity and mortality in Canada (and worldwide). Despite the established benefits of treatment with statins, most Canadians fail to achieve dyslipidemia targets (a risk factor for ASCVD).
  • The objective of this study was to examine current treatment patterns of lipid-lowering therapies for the management of low-density lipoprotein cholesterol (LDL-C) in patients with ASCVD.
  • This was a retrospective cohort study conducted using province-wide administrative health data from Alberta, Canada. Datasets used included health services, pharmaceutical, and laboratory data, in addition to the Alberta population registry. The study population consisted of individuals aged 18 years or older diagnosed with ASCVD between 2011-2015, based on International Classification of Diseases (ICD) codes. The cohort was then restricted to individuals with an initial (index) LDL-C measurement after ASCVD diagnosis and at least one year of pre-index data and one year of follow-up data.

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High-Intensity Binge Drinking Linked to Abnormal Lipids and Liver Function Tests

MedicalResearch.com Interview with:

Falk W. Lohoff, MD Chief, Section on Clinical Genomics and Experimental Therapeutics (CGET) Lasker Clinical Research Scholar National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institutes of Health (NIH) Bethesda, MD 20892-1540

Dr. Lohoff

Falk W. Lohoff, MD
Chief, Section on Clinical Genomics and Experimental Therapeutics (CGET)
Lasker Clinical Research Scholar
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health (NIH)
Bethesda, MD 20892-1540 

MedicalResearch.com: What is the background for this study?

Response: More than 32 million adults in the United States report engaging in high-intensity binge drinking (consuming two- and three- times the traditional binge thresholds of 5 drinks per occasion for men and 4 drinks per occasion for women) and associated adverse health effects represent a significant public health problem in the US.

While alcohol consumption has been associated with changes in cardiovascular risk factors like high-density lipoprotein cholesterol (HDL-C) and triglycerides as well as liver function enzymes, previous studies were not able to study these associations among those reporting recent high-intensity binge drinking. We utilized a cross-sectional dataset containing both sufficiently detailed alcohol consumption data, cholesterol, and liver function enzyme levels to examine these associations. 

MedicalResearch.com: What are the main findings? 

Response: Our main finding showed high-intensity binge drinking was associated with a dose-dependent 2- to 8-fold increased odds for clinically high levels of HDL-C, total cholesterol, triglycerides, and all liver function enzymes (gamma-glutamytransferase, aspartate aminotransferase, and alanine aminotransferase). In a separate analysis of drinking patterns, we found each additional day of high-intensity binging also increased the odds of clinically high biomarkers. 

MedicalResearch.com: What should readers take away from your report?

Response: Our study highlights the possible negative cardiovascular and hepatic impact associated with high-intensity binge drinking. Given that high-intensity binge drinking is common on weekends, special events, and holidays, it is alarming that even one additional day of high-intensity binge drinking may increase cardiometabolic risk factor levels.

When combined with previous work showing normalization of cholesterol and liver enzyme levels with alcohol reduction, these findings suggest that drinking reduction intervention strategies aimed at reducing high-intensity binge drinking may be associated with improved health outcomes.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Our cross-sectional study evaluated only cardiometabolic risk factors. Therefore, future research is needed to examine the impact of high-intensity binge drinking on cardiometabolic disease outcomes, such as myocardial infarction, atherosclerosis, and stroke as well as liver disease. These findings need also to be replicated in larger, population-based cohorts.

MedicalResearch.com: Is there anything else you would like to add? 

Response: These findings emphasize the importance of future research evaluating the health impact of this increasingly common hazardous alcohol consumption pattern. Further, these data suggest that inquiring about recent high-intensity binge drinking may be useful in clinical settings if the elevated cholesterol and liver levels are present.

Disclosures: The authors have no disclosures relevant to the manuscript

This study was supported by the National Institute on Alcohol Abuse and Alcoholism

Citation:

 

Rosoff DB, Charlet K, Jung J, et al. Association of High-Intensity Binge Drinking With Lipid and Liver Function Enzyme Levels. JAMA Netw Open. Published online June 14, 20192(6):e195844. doi:10.1001/jamanetworkopen.2019.5844

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2735766 

 

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The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Statins May Double Risk of Diabetes

MedicalResearch.com Interview with:

Victoria A. Zigmont, PhD MPH Southern Connecticut State University/ Department of Public Health Assistant Professor New Haven, CT

Dr. Zigmont

Victoria A. Zigmont, PhD MPH
Southern Connecticut State University
Department of Public Health
Assistant Professor
New Haven, CT

MedicalResearch.com: What is the background for this study? What are the main findings? 

  • We were interested in conducting this study to better understand the diabetogenic risks (dysglycemia (measured using elevated HbA1c) and new diagnoses of diabetes) associated with statin use for everyday people in the general population.
  • We conducted a retrospective cohort study and compared new users of statins to equivalent nonusers of statins. All of the study participants had indications for statin use in their electronic medical records for the primary (patients without a history of cardiovascular disease (CVD)) or secondary prevention (patients who have had CVD) of CVD. This study used pharmacy and medical claims, and biometric data as well as data from a health survey.

MedicalResearch.com: What are the main findings?

Response: After adjusting for confounding factors (age, gender, education level, ethnicity, cholesterol and triglyceride readings, body mass index, waist circumference and the number of visits to the doctor) statin users had at least double the risk for developing type 2 diabetes mellitus compared to statin nonusers. Individuals who used statins for the longest period of time (more than 2 years) had an even greater risk (3 times greater) for developing type 2 diabetes mellitus, after adjusting for confounding factors.

MedicalResearch.com: What should readers take away from your report?

  • These study findings indicate that statin users should receive special guidance on diet and physical activity for diabetes prevention from their medical care team. These individuals should also receive close monitoring to detect changes in glucose metabolism.
  • Statins are a well-established way to prevent heart attacks and strokes. It could be harmful if patients stopped taking their statins, and they should talk to their physicians if they have concerns about side effects associated with their medications.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Further research is needed to understand which statins and doses lead to a greater risk of diabetes, and well as the impact of statins on human metabolism. Clinical studies testing new medications should report on the risks and benefits in addition to the desired clinical outcomes.

This study was conducted as part of my doctoral dissertation at the Ohio State University. I am now an assistant professor at Southern Connecticut State University (New Haven). The study co-authors were Drs. Susan Olivo-Marston (dissertation advisor), Abigail Shoben, Bo Lu, Steven Clinton, Randall Harris and Gail Kaye. 

Citation:

Victoria A. Zigmont, Abigail B. Shoben, Bo Lu, Gail L. Kaye, Steven K. Clinton, Randall E. Harris, Susan E. Olivo‐Marston. Statin users have an elevated risk of dysglycemia and new‐onset‐diabetes. Diabetes/Metabolism Research and Reviews, 2019; e3189 DOI: 1002/dmrr.3189

 

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The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Lowered Price of Repatha® (evolocumab) Translates to Cost Effectiveness for Range of Heart Conditions in Some High Risk Patients

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, 90095-1679

Dr. Gregg Fonarow

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?

Response: Last year, Amgen made the PCSK-9 inhibitor evolocumab available at a reduced list price of $5,850 per year This 60% reduction was aimed at improving patient access by lowering patient copays, especially for Medicare beneficiaries.

Additionally, the treatment landscape for PCSK9 inhibitors was further defined in 2018 when the American College of Cardiology/American Heart Association Multisociety Clinical Guideline on the Management of Blood Cholesterol recommended PCSK9 inhibitors for, among other patient populations, patients with very high-risk (VHR) ASCVD whose low-density lipoprotein cholesterol levels remain at 70 mg/dL or more  despite a heart-healthy lifestyle and treatment with standard background therapy.

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Eggs Should Be Eaten In Moderation – Higher Intake Linked to Increased Mortality

MedicalResearch.com Interview with:

Prof. Katherine Tucker PhD Director of the Center for Population Health Zuckerberg College of Health Sciences Lowell’s Biomedical and Nutritional Sciences UMass

Dr. Tucker

Prof. Katherine Tucker PhD
Director of the Center for Population Health
Zuckerberg College of Health Sciences
Lowell’s Biomedical and Nutritional Sciences
UMass

MedicalResearch.com: What is the background for this study? 

Response: Cholesterol was excluded from the recent dietary guidelines, but research remains unclear about eggs and cholesterol on health.

MedicalResearch.com: What are the main findings? Why is the advice about the benefits/harms regarding egg intake often so conflicting?

Response: Higher egg intake and cholesterol intake were related to increased risk of mortality. Individual observational studies can be confusing as the overall results depend on the baseline intake of the population and adjustment for confounders.  

MedicalResearch.com: What should readers take away from your report?

Response: Balance and moderation is the key. Complete avoidance of eggs and egg yolks is not recommended because they have healthy nutrients as well. Extremely high intake of any single food may lead to imbalances. 3-4 eggs a week appears healthy but intakes of multiple eggs/day are probably not a good idea.  

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We need to clarify what exactly it is about too many eggs that is causing the risk. Healthy metabolism depends on a complex interaction of nutrients.

No disclosures 

Citation:

Zhong VW, Van Horn L, Cornelis MC, et al. Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality. JAMA. 2019;321(11):1081–1095. doi:10.1001/jama.2019.1572

https://jamanetwork.com/journals/jama/article-abstract/2728487 

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The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Study Finds You Don’t Have To Fast Before Getting Your Lipids Measured

MedicalResearch.com Interview with:

Samia Mora, MD, MHSAssociate Physician, Brigham and Women's HospitalAssociate Professor of Medicine, Harvard Medical SchoolBrigham and Women's HospitalDepartment of MedicinePreventive MedicineBoston, MA 02115 

Dr. Mora

Samia Mora, MD, MHS
Associate Physician, Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
Brigham and Women’s Hospital
Department of Medicine
Preventive Medicine
Boston, MA 02115 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Lipid testing plays a major role in cardiovascular disease (CVD) risk screening, prediction, and treatment. In the past decade, several pivotal studies (including the Women’s Health Study, the Copenhagen City Heart Study, and the Copenhagen General Population Study) compared populations of individuals who had fasting lipid testing with populations of individuals who had nonfasting lipid testing, and found that non-fasting lipids were at least as good as fasting lipids in cardiovascular risk screening and predicting CVD risk.

To date, however, no study has examined the cardiovascular predictive value of lipids measured on the same individuals who had both fasting and nonfasting lipid testing. This is important because individual-level variability in fasting versus nonfasting lipids may not be captured when looking at population-level risk associations, and evidence from randomized studies is lacking. Furthermore, it is unclear whether substituting nonfasting lipids would misclassify cardiovascular risk for individuals who may be eligible for statin therapy.

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Cholesterol Levels in American Youth Improving, But Only Half Have Ideal Lipid Levels

MedicalResearch.com Interview with:

Amanda Marma Perak, MD, MSAssistant Professor of Pediatrics (Cardiology) and Preventive Medicine

Dr. Marma Perak

Amanda Marma Perak, MD, MS
Assistant Professor of Pediatrics (Cardiology) and
Preventive Medicine

MedicalResearch.com: What is the background for this study?

Response: Blood cholesterol is a critical initiator of atherosclerotic plaques in the arteries that can lead to heart attack in adulthood. It is well established that these changes in the blood vessels occur already in childhood. Thus, it is important to know the status of cholesterol levels in youth to inform public health efforts aimed at preventing cardiovascular disease in the population.

In the US there have been changes in childhood obesity prevalence (which may worsen cholesterol levels), the food supply (such as reduction of trans fats which may improve cholesterol levels), and other factors in recent years.

We therefore designed a study to examine trends in cholesterol levels among youth in recent years.

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Novel Lantibiotic Against C. diff Infections May Improve Lipid Profile

MedicalResearch.com Interview with:

Rajesh Kumar NV, Ph.D.Affiliation during the study:Senior Manager, Human Therapeutics Division,Intrexon Corporation, Germantown, MD, USA

Dr. Rajesh Kumar NV

Rajesh Kumar NV, Ph.D.
Affiliation during the study:
Senior Manager, Human Therapeutics Division,
Intrexon Corporation, Germantown, MD, USA
Current affiliation:
Translational Research Program Manager, Oncology Drug Discovery,
Department of Radiation Oncology and Molecular Radiation Sciences,
Johns Hopkins University School of Medicine
Baltimore, MD,  


MedicalResearch.com: What is the background for this study?

Response: Clostridium difficile is a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon. Clostridium difficile infection is the most frequent form of colitis in hospitals and nursing homes and affects millions of patients in the United States and abroad. Clostridium difficile associated disease (CDAD) is a global public health challenge where even mild to moderate infections at times can quickly progress to a fatal disease if not treated promptly.

OG253 is a novel lantibiotic in development for the treatment of CDAD. Lantibiotics are antimicrobial peptides whose chemical structure includes a bridge maintained by the non-canonical amino acid lanthionine. The primary objective of our study was to evaluate the repeated dose toxicokinetics and any possible side effects of OG253 as enteric-coated capsules following daily oral administrations of three different doses (6.75, 27 and 108 mg/day) for a single day or seven consecutive days in both genders of rats.

An enteric-coated capsule of OG253 was formulated in an attempt to circumvent the proteolytic degradation of OG253 in the upper digestive tract and specifically deliver this lantibiotic to the distal portion of the small intestine. Continue reading

Genetic Studies Can Help Determine How Low LDL Should Go With Treatment

Florian Kronenberg

Dr. Kronenberg

MedicalResearch.com Interview with:
Florian Kronenberg, MD
Division of Genetic Epidemiology
Department of Medical Genetics, Molecular and Clinical Pharmacology
Medical University of Innsbruck, Innsbruck, Austria

MedicalResearch.com: What is the background for this study?

Response: Lp(a) is one of the most prevalent lipoprotein risk factors for cardiovascular disease. Roughly 20% of the general Caucasian population have concentrations above 50 mg/dL and the 10% with the highest concentrations have a 2 to 3-fold increased risk for myocardial infarction.

There is strong evidence from genetic studies that high Lp(a) concentrations are causally related to cardiovascular outcomes. Until recently there was no drug available which lowers Lp(a) without any effects on other lipoproteins. This has recently changed by the development of drugs that block the production of Lp(a) in an impressive way. These drugs have to be studied in randomized controlled trials whether they not only lower Lp(a) concentrations but also cardiovascular outcomes. For the planning of such studies it is crucial to estimate the amount of Lp(a) lowering required to show a clinical benefit.

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Very Low LDL Cholesterol Associated with Hemorrhagic Stroke in Women

MedicalResearch.com Interview with:

Pamela M. Rist, ScDAssistant Professor of Medicine, Harvard Medical SchoolBrigham and Women's Hospital, Division of Preventive MedicineBoston, MA 02215 

Dr. Rist

Pamela M. Rist, ScD
Assistant Professor of Medicine, Harvard Medical School
Brigham and Women’s Hospital, Division of Preventive Medicine
Boston, MA 02215 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although hypercholesterolemia is a risk factor for ischemic stroke, some prior studies have observed an inverse association between total and low-density lipoprotein (LDL) cholesterol and risk of hemorrhagic stroke.  However, many studies were not able to study this association specifically among women.

Our main result was very low levels of low-density lipoprotein (LDL) cholesterol or low levels of triglycerides were associated with an increased risk of hemorrhagic stroke among women. Continue reading

Dietary Cholesterol from Eggs Linked to Cardiovascular and All-Cause Mortality

MedicalResearch.com Interview with:

Victor Wenze Zhong, Ph.D.Postdoctoral fellowDepartment of Preventive MedicineFeinberg School of MedicineNorthwestern University 680 N Lake Shore Dr, Suite 1400Chicago, IL 60611

Dr. Zhong

Victor Wenze Zhong, Ph.D.
Postdoctoral fellow
Department of Preventive Medicine
Feinberg School of Medicine
Northwestern University
Chicago, IL 60611 

MedicalResearch.com: What is the background for this study?

Response: Dietary cholesterol is a common nutrient in human diet. Eggs, specially egg yolks, are the single richest source of dietary cholesterol among all commonly consumed foods. The associations between dietary cholesterol consumption and cardiovascular disease and mortality remain controversial despite decades of research. Eating less than 300 mg of dietary cholesterol per day was the guideline recommendation before 2015. However, the most recent 2015-2020 Dietary Guidelines for Americans no longer include a daily consumption limit for dietary cholesterol and recommend weekly egg consumption as part of the healthy US-style eating pattern. Whether these recommendations are appropriate have been intensely debated.

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Even with Controlled LDL-Cholesterol, PCI Stent Patients Have Residual Inflammatory Risk

MedicalResearch.com Interview with:

Dr. George Dangas MD PhDProfessor of Medicine, CardiologyMount Sinai Health System

Dr. Dangas

Dr. George Dangas MD PhD
Professor of Medicine, Cardiology
Mount Sinai Health System

MedicalResearch.com: What is the background for this study?

Response: Widespread use of statins targeted to decrease levels of low density lipoprotein cholesterol (LDL-C) below 70mg/dL are recommended by guidelines. However, residual cholesterol risk may only be one part of the residual risk equation. Indeed, Biological inflammation has long been known as a pathophysiological mechanism of atherosclerosis and the recent CANTOS trial opened new therapeutic perspective by demonstrating that inflammation modulation via selective interleukin-1β inhibition could result in improved diagnosis in patients with coronary artery disease.

However, the prevalence and impact of a residual inflammatory biological syndrome in patients with controlled cholesterol risk is unclear. Continue reading

Genetic Evidence Suggests New LDL-C Lowering Drug May Decrease Cardiovascular Events and Have Additive Effect with Statins

MedicalResearch.com Interview with:

Brian A Ference, MD, MPhil, MSc, FACC, FESCProfessor and Director of Research in Translational TherapeuticsExecutive Director, Centre for Naturally Randomized TrialsStrangeways Research LaboratoryUniversity of CambridgeCambridge, UK

Dr. Ference

Brian A Ference, MD, MPhil, MSc, FACC, FESC
Professor and Director of Research in Translational Therapeutics
Executive Director, Centre for Naturally Randomized Trials
Strangeways Research Laboratory
University of Cambridge
Cambridge, UK

MedicalResearch.com: What is the background for this study?

Response: Bempedoic acid is a novel therapy currently in development that lowers LDL-C by inhibiting ATP-citrate lyase, an enzyme in the same cholesterol biosynthesis pathway as HMG-CoA reductase (the target of stains).  However, whether lowering LDL-C by inhibiting ATP-citrate lyase will reduce the risk of cardiovascular events to the same extent as lowering LDL-C by inhibiting HMG-CoA reductase with a statin is unknown.

We conducted a “naturally randomized trial” using Mendelian randomization in more than 650,000 participants who experienced more than 100,000 cardiovascular events to evaluate the potential clinical benefit of lowering LDL-C by inhibiting ATP-citrate lyase as compared to lowering LDL-C by inhibiting HMG-CoA reductase.

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Bempedoic Acid Lowers LDL When Statins Alone Aren’t Enough

MedicalResearch.com Interview with:

Prof. Kosh Ray, MB ChB, MD, MPhil Faculty of Medicine, School of Public HealthChair in Public Health (Clinical)Imperial College London

Dr. Ray

Prof. Kosh Ray, MB ChB, MD, MPhil
Faculty of Medicine, School of Public Health
Chair in Public Health (Clinical)
Imperial College London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bempedoic acid is the first in class of a new therapy for lowering LDL cholesterol. This is the largest and longest study to date with this therapy and involved about 2200 pts with patients with either established cardiovascular disease or familial hypercholestrolaemia and in whom LDL was > 70mg/dl or 1.8 mmol/L despite maximally tolerated statins. %0% were on high intensity statins and the majority of the rest on moderate intensity.

The aim was to show long term safety 1 year and efficacy at 24 weeks and at 1 year.  Continue reading

What Price Would Make Alirocumab (Praluent) Cost Effective for Lipid Control?

MedicalResearch.com Interview with:

Dhruv S. Kazi, MD, MSc, MS Associate Directo Richard A. and Susan F. Smith Center for Outcomes Research Boston MA 02215 Associate Director Cardiac Critical Care Unit Beth Israel Deaconess Medical Center

Dr. Kazi

Dhruv S. Kazi, MD, MSc, MS
Associate Director
Richard A. and Susan F. Smith Center for Outcomes Research
Boston MA 02215
Associate Director
Cardiac Critical Care Unit
Beth Israel Deaconess Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ODYSSEY Outcomes trial found that addition of alirocumab to statin therapy reduces the incidence of a composite of cardiovascular death, myocardial infarction, and stroke among patients with a recent history of a myocardial infarction and elevated low-density lipoprotein cholesterol.

We modeled the cost-effectiveness of alirocumab and found that, at the March 2018 price of the drug, it would not be cost-effective (either relative to statin alone or statin + ezetimibe) for this indication. We found that a large price-reduction would be required to meet the cost-effectiveness threshold of $100,000 per quality-adjusted life year. Shortly after the preliminary findings of this study were released, both manufacturers of PCSK9 inhibitors announced large price reductions in order to improve access to these drugs.

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Age, Gender and Drug Should Factor Into Statin Recommendation

MedicalResearch.com Interview with:

Prof. Dr. Milo Puhan Epidemiology, Biostatistics and Prevention Institute University of Zurich

Prof. Puhan

Prof. Dr. Milo Puhan
Epidemiology, Biostatistics and Prevention Institute
University of Zurich

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The use of statins for primary cardiovascular prevention is controversial and there is a debate at what risks statins provide more benefits than harms.

Current guidelines recommend statins if the 10 year risk for cardiovascular events is above 7.5 to 10% and they do not distinguish between men and women, different age groups and different statins.

We found in our study that the benefits of statins exceeds the harms if the 10 year risk for cardiovascular events is above 14% for middle aged mean (40-44 years) but even higher for older age groups, and women.

In addition, the benefit harm balance varies substantially between different statins with atorvastatin providing the best benefit harm balance.

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Psoriasis: Experimental Use of Lipid Molecule to Supress Inflammation

MedicalResearch.com Interview with:

Wendy Bollag, PhD, FAHA Professor of Physiology VA Research Career Scientist Augusta University, Georgia

Dr. Bollag

Wendy Bollag, PhD, FAHA
Professor of Physiology
VA Research Career Scientist
Augusta University, Georgia

MedicalResearch.com: What is the background for this study?

Response: We have previously shown that the lipid (fat) phosphatidylglycerol (PG) is able to inhibit rapidly growing keratinocytes (skin cells) and promote their maturation. We also found that PG can suppress skin inflammation.

Since the common skin disease psoriasis is characterized by inflammation and excessive growth and abnormal maturation of skin cells, we believed that PG might be useful as a treatment. However, the mechanism of its anti-inflammatory effect was unknown. PG in the lung has been found to inhibit inflammation induced by microbes or their components, which work by activating the innate immune system via binding to proteins called toll-like receptors (TLRs); however, psoriasis is not considered to be an infectious disease.

We hypothesized that PG would also inhibit inflammation induced by anti-microbial peptides that activate TLRs. Anti-microbial peptides, produced normally by the skin to protect against infection, are known to be excessively up-regulated in psoriatic skin.  Continue reading

Lowering Triglycerides and Cholesterol Could Reduce Heart Disease and Diabetes Risk

MedicalResearch.com Interview with:

Luca A. Lotta, MD, PhD Senior Clinical Investigator MRC Epidemiology Unit University of Cambridge

Dr. Lotta

Luca A. Lotta, MD, PhD
Senior Clinical Investigator
MRC Epidemiology Unit
University of Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

  • Drugs that enhance the breakdown of circulating triglycerides by activating lipoprotein lipase (LPL) are in pre-clinical or early-clinical development.
  • It is not known if these drugs will reduce heart attacks or diabetes risk when added to the current first line therapies (statins and other cholesterol-lowering agents).
  • Studying this would require large randomised controlled trials, which are expensive (millions of GBPs) and time-consuming (years).
  • Human genetic data can be used to provide supportive evidence of whether this therapy is likely to be effective by “simulating” a randomised controlled trial.
  • Our study used naturally occurring genetic variants in the general population (study of ~400,000 people) to address this.
  • Individuals with naturally-lower cholesterol due to their genetic makeup were used as model for cholesterol-lowering therapies (eg. Statins).
  • Individuals with naturally-lower triglycerides due to genetic variants in the LPL gene were used as model for these new triglyceride-lowering therapies.
  • We studied the risk of heart attacks and type 2 diabetes in people in different groups.

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When It Comes to LDL-C, “You Really Can’t Be Too Low”

MedicalResearch.com Interview with:

Marc S. Sabatine, MD, MPH  Chairman | TIMI Study Group  Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine Brigham and Women's Hospital  Professor of Medicine | Harvard Medical School

Dr. Marc Sabatine

Marc S. Sabatine, MD, MPH
Chairman | TIMI Study Group
Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine
Brigham and Women’s Hospital
Professor of Medicine | Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease.

The initial statin trials studied patients with high levels of LDL-C, and showed a benefit by lowering LDL-C.

We and others did studies in patients with so-called “average” levels of LDL-C (120-130 mg/dL), and also showed clinical benefit with lowering.

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Not All HDL Cholesterol is Good – Size Matters

MedicalResearch.com Interview with:

Samar R. El Khoudary, PhD, MPH, BPharm, FAHA Associate Professor, Epidemiology PITT Public Health Epidemiology Data Center University of Pittsburgh Pittsburgh, PA 15260 

Dr. El Khoudary

Samar R. El Khoudary, Ph.D., M.P.H. BPharm, FAHA
Associate Professor
Department of Epidemiology
University of Pittsburgh Graduate School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is based on the current measurements used to determine cardiovascular disease risk in postmenopausal women. Higher levels of HDL “good cholesterol” as measured by the widely available clinical test, HDL-Cholesterol, may not always be indicative of a lower risk of cardiovascular disease in postmenopausal women.

HDL is a family of particles found in the blood that vary in sizes, cholesterol contents and function. HDL particles can become dysfunctional under certain conditions such as chronic inflammation. HDL has traditionally been measured as the total cholesterol carried by the HDL particles, known as HDL cholesterol. HDL cholesterol, however, does not necessarily reflect the overall concentration, the uneven distribution, or the content and function of HDL particles.

We looked at 1,138 women aged 45 through 84 enrolled across the U.S. in the Multi-Ethnic Study of Atherosclerosis (MESA), a medical research study sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). MESA began in 1999 and is still following participants today. We assessed two specific measurements of HDL: the number and size of the HDL particles and total cholesterol carried by HDL particles. Our study also looked at how age when women transitioned into post menopause, and the amount of time since transitioning, may impact the expected cardio-protective associations of HDL measures.

Our study points out that the traditional measure of the good cholesterol, HDL cholesterol, fails to portray an accurate depiction of heart disease risk for postmenopausal women. We reported a harmful association between higher HDL cholesterol and atherosclerosis risk that was most evident in women with older age at menopause and who were greater than, or equal to, 10 years into post menopause. In contrast to HDL cholesterol, a higher concentration of total HDL particles was associated with lower risk of atherosclerosis. Additionally, having a high number of small HDL particles was found beneficial for postmenopausal women. These findings persist irrespective of age and how long it has been since women became postmenopausal.

On the other hand, large HDL particles are linked to an increased risk of cardiovascular disease close to menopause. Women are subject to a variety of physiological changes in their sex hormones, lipids, body fat deposition and vascular health as they transition through menopause. We are hypothesizing that the decrease of estrogen, a cardio-protective sex hormone, along with other metabolic changes, can trigger chronic inflammation over time, which may alter the quality of HDL particles. Future studies should test this hypothesis.

The study findings indicate that measuring size and number of HDL particles can better reflect the well-known cardio-protective features of the good cholesterol in postmenopausal women. Continue reading

Individuals With Very High Levels of Lipoprotein(a) May Benefit Most From LDL(a)-Lowering Drugs

MedicalResearch.com Interview with:

Dr. Stephen Burgess PhD Programme Leader at the Medical Research Council Biostatistics Unit University of Cambridge

Dr. Burgess

Dr. Stephen Burgess PhD
Programme Leader at the Medical Research Council Biostatistics Unit
University of Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Lipoprotein(a) is a lipoprotein subclass, and an important biomarker for coronary heart disease. As a clinical biomarker, it has a similar story to LDL-cholesterol (“bad” cholesterol), in that it is thought to be a causal risk factor for coronary heart disease, and so is a potential target for drug development. However, while drugs that lower LDL-cholesterol, such as statins, have been successful in reducing coronary heart disease risk, drugs that lower lipoprotein(a) have not as yet been successful. New drugs are currently in development that specifically target lipoprotein(a) and can lower lipoprotein(a) concentrations by 80-90%. We performed this study to investigate whether these drugs are likely to be successful in reducing coronary heart disease risk.

We compared individuals with naturally-occurring genetic variants that predispose them to a higher or lower lifetime concentration of lipoprotein(a) as a way of mimicking a randomized controlled trial. This approach has previously been undertaken for other biomarkers, including LDL-cholesterol. We found that having 10mg/dL lower genetically-predicted concentration of lipoprotein(a) was associated with a 5.8% reduction in coronary heart disease risk.

However, associations between genetically-predicted LDL-cholesterol and coronary heart disease risk are quantitatively much stronger than the proportional effect of LDL-cholesterol lowering on coronary heart disease risk as estimated by statin trials. This is because differences in genetic variants reflect lifelong changes in LDL-cholesterol, whereas statin trials only lower LDL-cholesterol for a few years. Hence, using the ratio between the genetic and trial estimates for LDL-cholesterol, we estimate that lowering lipoprotein(a) by 10mg/dL in a short-term clinical trial would only reduce coronary heart disease risk by 2.7%. To obtain the same reduction in coronary heart disease risk of around 20% as observed in statin trials, lipoprotein(a) would have to be lowered by around 100mg/dL. This explains why previous trials of less specific and less potent lipoprotein(a)-lowering drugs have failed to demonstrate benefit.

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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

African Americans Less Likely To Be Treated With Statins

MedicalResearch.com Interview with:

Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC

Dr. Nanna

Michael G. Nanna, MD
Fellow, Division of Cardiology
Duke University Medical Center
Durham, NC

MedicalResearch.com: What is the background for this study?

Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case.

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LPA Gene Variants Linked To Cardiac Events Despite Statins

MedicalResearch.com Interview with:

Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203

Dr. Wei-Qi Wei

Wei-Qi Wei, MD, PhD
Assistant Professor
Department of Biomedical Informatics
Vanderbilt University
Nashville, TN 37203

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events.

Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant.

We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  Continue reading

Patients With Highest LDL Levels Benefit Most From Lipid-Lowering Drugs

MedicalResearch.com Interview with:

Dr. Jennifer Robinson, MD MPH professor of epidemiology, University of Iowa College of Public Health. CREDIT Tom Langdon

Dr. Robinson

Dr. Jennifer Robinson, MD MPH
Professor, Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
University of Iowa

MedicalResearch.com: What is the background for this study?

Response: Compared to previous placebo-controlled statin trials, the FOURIER trial where all patients were on high or moderate intensity statin, had no reduction in cardiovascular or total mortality and the reduction in cardiovascular events was less than expected.  However, other PCSK9 inhibitor trials performed in populations with higher baseline low density lipoprotein cholesterol (LDL-C) had cardiovascular risk reductions similar to that in the statin trails.

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Very High ‘Good Cholesterol’ HDL Linked To Increased Risk of Infections

MedicalResearch.com Interview with:

Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark

Prof. Nordestgaard

Børge G. Nordestgaard, MD, DMSc
Professor, University of Copenhagen
Chief Physician, Dept. Clinical Biochemistry
Herlev and Gentofte Hospital
Copenhagen University Hospital, Denmark 

MedicalResearch.com: What is the background for this study?

Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease.

Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large.

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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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